Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data.

Authors:

BMJ 2011 Feb 15;342:d548. Epub 2011 Feb 15.

Objective: To use genetic variants as unconfounded proxies of C reactive protein concentration to study its causal role in coronary heart disease.

Design: Mendelian randomisation meta-analysis of individual participant data from 47 epidemiological studies in 15 countries.

Participants: 194 418 participants, including 46 557 patients with prevalent or incident coronary heart disease. Information was available on four CRP gene tagging single nucleotide polymorphisms (rs3093077, rs1205, rs1130864, rs1800947), concentration of C reactive protein, and levels of other risk factors.

Main Outcome Measures: Risk ratios for coronary heart disease associated with genetically raised C reactive protein versus risk ratios with equivalent differences in C reactive protein concentration itself, adjusted for conventional risk factors and variability in risk factor levels within individuals.

Results: CRP variants were each associated with up to 30% per allele difference in concentration of C reactive protein (P<10(-34)) and were unrelated to other risk factors. Risk ratios for coronary heart disease per additional copy of an allele associated with raised C reactive protein were 0.93 (95% confidence interval 0.87 to 1.00) for rs3093077; 1.00 (0.98 to 1.02) for rs1205; 0.98 (0.96 to 1.00) for rs1130864; and 0.99 (0.94 to 1.03) for rs1800947. In a combined analysis, the risk ratio for coronary heart disease was 1.00 (0.90 to 1.13) per 1 SD higher genetically raised natural log (ln) concentration of C reactive protein. The genetic findings were discordant with the risk ratio observed for coronary heart disease of 1.33 (1.23 to 1.43) per 1 SD higher circulating ln concentration of C reactive protein in prospective studies (P=0.001 for difference).

Conclusion: Human genetic data indicate that C reactive protein concentration itself is unlikely to be even a modest causal factor in coronary heart disease.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039696PMC
http://dx.doi.org/10.1136/bmj.d548DOI Listing
February 2011
38 Reads

Publication Analysis

Top Keywords

reactive protein
24
coronary heart
16
heart disease
12
mendelian randomisation
8
participant data
8
concentration reactive
8
risk ratios
8
protein concentration
8
individual participant
8
protein
6
reactive
5
risk
5
protein levels
4
risk factorsmain
4
measures risk
4
outcome measures
4
factorsmain outcome
4
rs1800947 concentration
4
levels risk
4
polymorphisms rs3093077
4

Similar Publications